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A pioneering new clinical collaboration between a Cambridge start-up specialised in gut bacteria, and Cancer Care UK, is hoping to transform the approach to treating malignant tumours. Founded in 2016, Microbiotica has received backing from several venture capital funds to conduct its research trials with Cambridge University Hospitals.

Advances in our Understanding of the Microbiome

The complexity of gut bacteria, known as the microbiome, has become increasingly evident, and its role has been recognised in a host of inflammatory diseases, as well as mental diseases such as depression. In recent years faecal transplants have already been used to treat antibiotic-resistant Clostridioides Difficile infections, that have caused many deaths among hospital patients with compromised immune systems.

Even more intriguing, however, have been advances in understanding the role played by the microbiome in shaping our immune response to cancer and cancer treatments. The microbiome varies from one individual to another, and in combination with their genes, it is believed to be one of the major causes of why one patient might respond well to treatment, while another suffers debilitating side-effects.

Just like the human genome, the race is on to map the genomes of different species of gut bacteria in order to understand how they can be weaponised against cancer and other diseases. Faecal transplants, which in a small number of cases have caused death by also transplanting incurable pathogens, have long been viewed as a necessary but primitive approach that are only a prelude to far more effective outcomes. Given the sheer complexity of the endeavour, it is no surprise that research is coming of age at a time when huge advances have been made in machine learning and computing power.

“Each of us is host to trillions of bacteria in our guts, weighing up to 2.5 kilos,” Mike Romanos, CEO, and himself a seasoned researcher, explained to Innovation Origins. “Those trillions are on average made up of two to three hundred species out of a possible 1300 or so, with East Asians having noticeably rich and varied microbiomes and Americans of European descent having the most limited.”

Analysing the genomes of these bacteria, as well as their many sub-strains, in order to understand how they interact and modulate our immune system is only part of the challenge. Before that can be done, it requires technology that can extract, isolate, and sequence the genomes of samples, while keeping fragile cultures alive at a scale and speed that makes Microbiotica an outlier in its field.

“Thanks to a decade of pioneering work by Trevor Lawley at the Sanger institute, which is famous among other things for sequencing 40% of the human genome, we were well ahead of the game at the outset,” said Romanos. “His research made it possible to isolate the individual bacteria and sequence their entire genomes.”

Microbiotica boasts the world’s biggest dataset of gut bacteria species together with their genome sequences, and it has also discovered previously undetected bacteria. Combined with its technological knowhow it can now conduct rigorous and unrivalled research at an industrial scale. It is able to take faecal samples from patients participating in clinical trials in many different areas of medicine, and use its databank to produce analyses that are 100% accurate.

“We can conduct shotgun sequencing from stool samples, and map the gut bacteria and its entire genome for individual patients in short time, in a way our rivals simple can’t,” Romanos added. “We have done plenty of benchmarking, and discovered our rivals are often missing up to half the gut bacteria in their research.”

In an ongoing trial with Genotech, the company has already successfully discovered biomarkers in patients suffering from IBD which can determine whether they will respond positively to certain treatments. The latest oncology collaboration with Cancer Care UK and Cambridge University Hospitals, aims to build on this type of research, and take it a step further.

Increasing the Efficacy of new Cancer Treatments

Some cancers manage to hide from the immune system by triggering what are known as checkpoints in the immune system, thereby switching off an attack directed against them. In recent years a number of new cancer treatments have been developed known as checkpoint inhibitors. One such example is Pembrolizumab. These drugs can restore the immune system and direct it to attack the cancer. Inoperable cancers have been treated very effectively as a result, sometimes withcomplete remission.

Successful immune responses, however, occur in only 30% to 50% of the patients treated, depending on the cancer. It is now hoped that during treatment, co-therapies developed by the likes of Microbiotica, could broaden the effectiveness of these drugs by either finding new ways to modulate immune responses, or by enabling the selection of patients ahead of treatment who it is known will respond well by identifying key biomarkers that determine their immune response.

World Class Team and Future Revenue

Microbiotica was also cofounded by Cambridge Professor, Gordon Dougan, who has previously been a key player in major drug developments with pharmaceutical giants such as GSK. A former WHO advisor and world authority on epidemics and vaccine developments, he has also given his personal take on the current epidemic. According to Ramonos, they are also assessing whether they might have a role to play in helping to stratify patient responses to COVID-19 and future treatments, which have already been shown to be highly individualistic.

There is no shortage of potential partners and investors. The current oncological research being pioneered by Microbiotica is partly funded by venture capital, in particular Cambridge Innovation Capital, which is all too well aware that one checkpoint inhibitor drug alone, known as Keytruda, has an annual revenue of 10 billion dollars. Hence a treatment developed by Microbiotica that could broaden the effectiveness and application of this and other similar drugs, would immediately be able to tap into huge revenue streams.

Outcomes and Cancer Targets

It is hoped that one of the principal outcomes of Microbiotica’s collaboration with Cancer Care UK and Cambridge University Hospitals will be to identify specific gut bacterial signatures, and better understand how they assist or reduce the efficacy or side effects of treatments in individual patients.

The clinical studies will involve thousands of patients, making it one of the most rigorous ever conducted in this new area of medicine. In addition to identifying biomarkers, they will also be aiming to cultivate new co-therapies using live bacterial products, derived from the microbiome, which will directly assist the potency of other treatments and diminish, or entirely prevent, some of the often debilitating side effects. The cancers targeted by the research will include melanoma, nonsmall cell lung cancer, and renal cancer.

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